Meiotic arrest and spindle defects are associated with altered KIF11 expression in porcine oocytes

Abstract

Kinesin superfamily proteins (KIFs) act as molecular motors and are involved in material transport along microtubules to maintain normal cellular functions. KIF11 (also named kinesin-5, Eg5, and KSP) is a plus-end-directed homotetrameric kinesin that regulates spindle formation for actuate chromosomal separation during mitosis. However, the roles of KIF11 in meiosis are still unclear. In this study, we investigated the regulatory functions of KIF11 during porcine oocyte maturation. The results indicated that KIF11 was expressed in different stages during porcine oocyte meiosis. Inhibition of KIF11 activity led to the failure of the first polar body extrusion, and we found that cell cycle progression was disturbed, which was confirmed by the decreased Cdc2 expression. Furthermore, inhibition of KIF11 resulted in decreased tubulin acetylation and caused sequential disruption of the spindle assembly and chromosome alignment. We also found that in postovulatory aging porcine oocytes, the KIF11 expression was altered, indicating that KIF11 was involved with aging-induced spindle disorganization. In summary, our results showed that KIF11 regulated the cell cycle and tubulin acetylation related spindle formation in porcine oocyte meiosis. Environ. Mol. Mutagen. 59:805-812, 2018. © 2018 Wiley Periodicals, Inc.

PRC1 is a critical regulator for anaphase spindle midzone assembly and cytokinesis in mouse oocyte meiosis

“…Inhibition of different histone deacetylases such as HDAC3, HDAC6, and HDAC11 all could cause spindle defects in oocytes [46][47][48]. Besides, kinesins such as Kif11, Kif17, and Kif18 are shown to affect spindle organization through their effects on microtubule acetylation level during mouse oocyte maturation [49][50][51]. Our results reveal that PRC1 KD resulted in increased acetylation of microtubules in mouse oocytes, while the supplementation of PRC1 mRNA could reduce tubulin acetylation to the normal level, which further confirmed the role of PRC1 in formation of the spindle midzone in mouse oocytes.…”

“…Kinesins are crucial for spindle assembly, chromosome segregation, and cell division [52]. For example, our recent study indicated that KIF11 regulates meiotic spindle formation and chromosome alignment during porcine oocyte meiosis [49]. Depleting ZEN-4 (MKLP1 homolog, a member of the kinesin-6 family) leads to diminished midzone microtubule bundles in C. elegans, [6] while KIF4 maintains a constant midzone length in HeLa cells for normal bipolar cytokinesis [3].…”

“…We collected the oocyte samples after 9 h of culture. NuPAGE LDS sample buffer (49) was used to lyse the oocytes (about 150-180) at 90°C for 10 min. Proteins were separated by sodium dodecyl sulfate/polyacrylamide gel electrophoresis at 150 V for 90 min, and then transferred to a polyvinylidene fluoride membrane (Millipore, Billerica, MA, USA) at 20 V for 80 min.…”

Kinesin-5 Eg5 is essential for spindle assembly and chromosome alignment of mouse spermatocytes

“…Eg5 inhibition leads to the collapse of meiosis II spindles and chromosome missegregation in mammalian oocytes [30]. Eg5 is expressed in all developmental stages during porcine oocyte meiosis, and its inhibition strongly delays meiotic progression due to the reduction of Cdc2 phosphorylation with its dose-dependent property [53]. Previous studies have revealed that kinesin-5 motors regulate chromosome alignment in mitotic cells.…”

SIRT2 Inhibition Results in Meiotic Arrest, Mitochondrial Dysfunction, and Disturbance of Redox Homeostasis during Bovine Oocyte Maturation

“…Mechanistically, our results suggest that SIRT2 mediate spindle/chromosome organization by deacetylating α-tubulin and histone H4K16. Spindle defects are closely associated with meiotic arrest [35]. Bipolar spindle assembly and function require normal microtubule dynamics [36].…”